Seizure pathways change on circadian and slower timescales in individual patients with focal epilepsy

Personalised medicine requires that treatments adapt to not only the patient, but changing factors within each individual. Although epilepsy is a dynamic disorder that is characterised by pathological fluctuations in brain state, surprisingly little is known about whether and how seizures vary in the same patient. We quantitatively compared within-patient seizure network dynamics using intracranial recordings of over 500 seizures from 31 patients with focal epilepsy (mean 16.5 seizures/patient). In all patients, we found variability in seizure paths through the space of possible network dynamics, producing either a spectrum or clusters of different dynamics. Seizures with similar pathways tended to occur closer together in time, and a simple model suggested that seizure pathways change on circadian and/or slower timescales in the majority of patients. These temporal relationships occurred independent of whether the patient underwent antiepileptic medication reduction. Our results suggest that various modulatory processes, operating at different timescales, shape within-patient seizure dynamics, leading to variable seizure pathways that may require tailored treatment approaches.

[1]  J. Régis,et al.  The role of corticothalamic coupling in human temporal lobe epilepsy. , 2006, Brain : a journal of neurology.

[2]  Laura A. Ewell,et al.  Brain State Is a Major Factor in Preseizure Hippocampal Network Activity and Influences Success of Seizure Intervention , 2015, The Journal of Neuroscience.

[3]  Viktor K. Jirsa,et al.  Predicting the spatiotemporal diversity of seizure propagation and termination in human focal epilepsy , 2017, Nature Communications.

[4]  Graeme Jackson,et al.  The peri-ictal state: cortical excitability changes within 24 h of a seizure. , 2009, Brain : a journal of neurology.

[5]  F. Wendling,et al.  Extraction of spatio-temporal signatures from depth EEG seizure signals based on objective matching in warped vectorial observations , 1996, IEEE Transactions on Biomedical Engineering.

[6]  P. Legendre,et al.  Statistical methods for temporal and space–time analysis of community composition data† , 2014, Proceedings of the Royal Society B: Biological Sciences.

[7]  D. Bassett,et al.  Recurring Functional Interactions Predict Network Architecture of Interictal and Ictal States in Neocortical Epilepsy , 2016, eNeuro.

[8]  Brian Litt,et al.  Dynamic Network Drivers of Seizure Generation, Propagation and Termination in Human Neocortical Epilepsy , 2014, PLoS Comput. Biol..

[9]  R. Duckrow,et al.  Subclinical seizures during intracranial EEG recording: Are they clinically significant? , 2014, Epilepsy Research.

[10]  Marcus Kaiser,et al.  Mechanisms underlying different onset patterns of focal seizures , 2016, PLoS Comput. Biol..

[11]  Haesun Park,et al.  Algorithms for nonnegative matrix and tensor factorizations: a unified view based on block coordinate descent framework , 2014, J. Glob. Optim..

[12]  Kaspar Anton Schindler,et al.  Increasing synchronization may promote seizure termination: Evidence from status epilepticus , 2007, Clinical Neurophysiology.

[13]  Terence O'Brien,et al.  Human focal seizures are characterized by populations of fixed duration and interval , 2016, Epilepsia.

[14]  J Gotman,et al.  Segmentation and classification of EEG during epileptic seizures. , 1998, Electroencephalography and clinical neurophysiology.

[15]  Brian Litt,et al.  A multimodal platform for cloud-based collaborative research , 2013, 2013 6th International IEEE/EMBS Conference on Neural Engineering (NER).

[16]  Gregory A Worrell,et al.  Lateralization of mesial temporal lobe epilepsy with chronic ambulatory electrocorticography , 2015, Epilepsia.

[17]  Kaspar Anton Schindler,et al.  Estimation of brain network ictogenicity predicts outcome from epilepsy surgery , 2016, Scientific Reports.

[18]  Klaus Lehnertz,et al.  Evolving functional network properties and synchronizability during human epileptic seizures. , 2008, Chaos.

[19]  N. Crone,et al.  Network dynamics of the brain and influence of the epileptic seizure onset zone , 2014, Proceedings of the National Academy of Sciences.

[20]  M. Walker,et al.  Do seizures in patients with refractory epilepsy vary between wakefulness and sleep? , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[21]  R. Yuste,et al.  Evidence of an inhibitory restraint of seizure activity in humans , 2012, Nature Communications.

[22]  Kaspar Anton Schindler,et al.  Forbidden ordinal patterns of periictal intracranial EEG indicate deterministic dynamics in human epileptic seizures , 2011, Epilepsia.

[23]  G. Ermentrout,et al.  Gamma rhythms and beta rhythms have different synchronization properties. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[24]  P. Crandall,et al.  Falsely Localizing Ictal Onsets with Depth EEG Telemetry During Anticonvulsant Withdrawal , 1983, Epilepsia.

[25]  D. Hasselquist,et al.  No evidence that carotenoid pigments boost either immune or antioxidant defenses in a songbird , 2018, Nature Communications.

[26]  H. Lüders,et al.  Presurgical evaluation of epilepsy. , 2001, Brain : a journal of neurology.

[27]  M. Kramer,et al.  Emergent network topology at seizure onset in humans , 2008, Epilepsy Research.

[28]  A. Loudon,et al.  Clocking in to immunity , 2018, Nature Reviews Immunology.

[29]  Kathryn A Davis,et al.  Temporal behavior of seizures and interictal bursts in prolonged intracranial recordings from epileptic canines , 2016, Epilepsia.

[30]  Evan M. Gordon,et al.  Long-term neural and physiological phenotyping of a single human , 2015, Nature Communications.

[31]  Jean Gotman,et al.  Prediction of secondary generalization from a focal onset seizure in intracerebral EEG , 2018, Clinical Neurophysiology.

[32]  J. Bellanger,et al.  Epileptic fast intracerebral EEG activity: evidence for spatial decorrelation at seizure onset. , 2003, Brain : a journal of neurology.

[33]  Gonzalo Alarcón,et al.  Prognostic value of intracranial seizure onset patterns for surgical outcome of the treatment of epilepsy , 2015, Clinical Neurophysiology.

[34]  N. Mantel The detection of disease clustering and a generalized regression approach. , 1967, Cancer research.

[35]  Brian Litt,et al.  Virtual Cortical Resection Reveals Push-Pull Network Control Preceding Seizure Evolution , 2016, Neuron.

[36]  Andreas Schulze-Bonhage,et al.  Quantifying antiepileptic drug effects using intrinsic excitability measures , 2016, Epilepsia.

[37]  Josemir W Sander,et al.  The relation between cortisol and functional connectivity in people with and without stress‐sensitive epilepsy , 2017, Epilepsia.

[38]  Joseph R. Madsen,et al.  Microscale spatiotemporal dynamics during neocortical propagation of human focal seizures , 2015, NeuroImage.

[39]  Kathryn A. Davis,et al.  Data integration: Combined imaging and electrophysiology data in the cloud , 2016, NeuroImage.

[40]  Robert Tibshirani,et al.  Estimating the number of clusters in a data set via the gap statistic , 2000 .

[41]  Sydney S Cash,et al.  Ictal and preictal power changes outside of the seizure focus correlate with seizure generalization , 2018, Epilepsia.

[42]  F Wendling,et al.  A method to quantify invariant information in depth-recorded epileptic seizures. , 1997, Electroencephalography and clinical neurophysiology.

[43]  C. Napolitano,et al.  Changing patterns of propagation in a super-refractory status of the temporal lobe. Over 900 seizures recorded over nearly one year☆ , 2013, Epilepsy & Behavior Case Reports.

[44]  Graeme D. Jackson,et al.  Cortical excitability and Refractory epilepsy: a Three-Year longitudinal Transcranial Magnetic Stimulation Study , 2013, Int. J. Neural Syst..

[45]  Haesun Park,et al.  Fast Nonnegative Matrix Factorization: An Active-Set-Like Method and Comparisons , 2011, SIAM J. Sci. Comput..

[46]  Kaspar Anton Schindler,et al.  Assessing seizure dynamics by analysing the correlation structure of multichannel intracranial EEG. , 2006, Brain : a journal of neurology.

[47]  S. Chiba,et al.  Dynamic programming algorithm optimization for spoken word recognition , 1978 .

[48]  A. Bardy Reduction of antiepileptic drug dosage for monitoring epileptic seizures , 1992, Acta neurologica Scandinavica.

[49]  F. Wendling,et al.  Time-frequency matching of warped depth-EEG seizure observations , 1999, IEEE Transactions on Biomedical Engineering.

[50]  Siqi Wu,et al.  Stability-driven nonnegative matrix factorization to interpret spatial gene expression and build local gene networks , 2016, Proceedings of the National Academy of Sciences.

[51]  Sydney S Cash,et al.  Slow Spatial Recruitment of Neocortex during Secondarily Generalized Seizures and Its Relation to Surgical Outcome , 2015, The Journal of Neuroscience.

[52]  Emily A. Mirro,et al.  Multi-day rhythms modulate seizure risk in epilepsy , 2018, Nature Communications.

[53]  J. Gotman,et al.  Effects of Drug Withdrawal on Location of Seizure Onset , 1986, Epilepsia.

[54]  Dean R. Freestone,et al.  A forward-looking review of seizure prediction , 2017, Current opinion in neurology.

[55]  D. Plenz,et al.  Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle , 2015, Proceedings of the National Academy of Sciences.

[56]  Frank Marten,et al.  Characterising the dynamics of EEG waveforms as the path through parameter space of a neural mass model: Application to epilepsy seizure evolution , 2012, NeuroImage.

[57]  Kaspar Anton Schindler,et al.  A Systems-Level Approach to Human Epileptic Seizures , 2012, Neuroinformatics.

[58]  R. Mattson,et al.  Ictal Effects of Anticonvulsant Medication Withdrawal in Epileptic Patients , 1981, Epilepsia.

[59]  F. Chowdhury,et al.  Supplementary code and visualisations for "Seizure pathways change on circadian and slower timescales in individual patients with focal epilepsy" , 2020 .

[60]  T. Loddenkemper,et al.  Chronopharmacology of Anti-Convulsive Therapy , 2013, Current Neurology and Neuroscience Reports.

[61]  M. Kramer,et al.  Epilepsy as a Disorder of Cortical Network Organization , 2012, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[62]  J. Régis,et al.  Enhanced EEG functional connectivity in mesial temporal lobe epilepsy , 2008, Epilepsy Research.

[63]  David B. Grayden,et al.  Estimation of effective connectivity via data-driven neural modeling , 2014, Front. Neurosci..

[64]  W. Stacey,et al.  On the nature of seizure dynamics. , 2014, Brain : a journal of neurology.

[65]  Marcus Kaiser,et al.  Computational modeling of neurostimulation in brain diseases. , 2015, Progress in brain research.

[66]  John S. Duncan,et al.  Seizure pathways change on circadian and slower timescales in individual patients with focal epilepsy , 2019, Proceedings of the National Academy of Sciences.

[67]  Andrea Facchinetti,et al.  Combining continuous glucose monitoring and insulin pumps to automatically tune the basal insulin infusion in diabetes therapy: a review , 2019, BioMedical Engineering OnLine.

[68]  Oren Sagher,et al.  Variability in the location of high frequency oscillations during prolonged intracranial EEG recordings , 2018, Nature Communications.

[69]  Kensuke Kawai,et al.  State-dependent precursors of seizures in correlation-based functional networks of electrocorticograms of patients with temporal lobe epilepsy , 2012, Neurological Sciences.

[70]  H. Sebastian Seung,et al.  Learning the parts of objects by non-negative matrix factorization , 1999, Nature.

[71]  Levin Kuhlmann,et al.  The circadian profile of epilepsy improves seizure forecasting , 2017, Brain : a journal of neurology.

[72]  M. Kramer,et al.  Coalescence and Fragmentation of Cortical Networks during Focal Seizures , 2010, The Journal of Neuroscience.

[73]  Karl J. Friston,et al.  A systematic framework for functional connectivity measures , 2014, Front. Neurosci..

[74]  Graeme D Jackson,et al.  Predicting seizure control: Cortical excitability and antiepileptic medication , 2010, Annals of neurology.

[75]  P. Pennell,et al.  Neuroendocrine considerations in the treatment of men and women with epilepsy , 2013, The Lancet Neurology.

[76]  C. Bazil Seizure modulation by sleep and sleep state , 2019, Brain Research.

[77]  Rafael Yuste,et al.  Reliable and Elastic Propagation of Cortical Seizures In Vivo. , 2017, Cell reports.

[78]  Levin Kuhlmann,et al.  Seizure pathways: A model-based investigation , 2018, PLoS Comput. Biol..

[79]  Grant M. Fiddyment,et al.  Human seizures couple across spatial scales through travelling wave dynamics , 2017, Nature Communications.

[80]  M. Seeck,et al.  Recurrent secondary generalization in frontal lobe epilepsy: Predictors and a potential link to surgical outcome? , 2015, Epilepsia.

[81]  E. Taubøll,et al.  Interactions between hormones and epilepsy , 2015, Seizure.

[82]  J. H. Cross,et al.  Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology , 2017, Epilepsia.

[83]  Charu C. Aggarwal,et al.  On the Surprising Behavior of Distance Metrics in High Dimensional Spaces , 2001, ICDT.

[84]  Pablo A. Iglesias,et al.  Control theory in biology and medicine - Introduction to the special issue , 2019, Biol. Cybern..

[85]  Danielle S Bassett,et al.  Characterizing the role of the structural connectome in seizure dynamics. , 2019, Brain : a journal of neurology.

[86]  E. Halgren,et al.  Single-neuron dynamics in human focal epilepsy , 2011, Nature Neuroscience.

[87]  F. Wendling,et al.  Mise en correspondance de relations inter-structures lors de crises d'épilepsie , 2002 .

[88]  S. Spencer Neural Networks in Human Epilepsy: Evidence of and Implications for Treatment , 2002, Epilepsia.

[89]  G. Alarcón,et al.  Power spectrum and intracranial EEG patterns at seizure onset in partial epilepsy. , 1995, Electroencephalography and clinical neurophysiology.

[90]  T S Walczak,et al.  Effects of Sleep and Sleep Stage on Epileptic and Nonepileptic Seizures , 1997, Epilepsia.

[91]  M. Avoli,et al.  Neurosteroids — Endogenous Regulators of Seizure Susceptibility and Role in the Treatment of Epilepsy -- Jasper's Basic Mechanisms of the Epilepsies , 2012 .

[92]  C. Harden,et al.  A Treatment Approach to Catamenial Epilepsy , 2016, Current Treatment Options in Neurology.

[93]  Ankit N Khambhati,et al.  Virtual resection predicts surgical outcome for drug-resistant epilepsy. , 2019, Brain : a journal of neurology.

[94]  Fabrice Wendling,et al.  Extraction of reproducible seizure patterns based on EEG scalp correlations , 2007, Biomed. Signal Process. Control..

[95]  Brian Litt,et al.  Virtual cortical resection reveals push-pull network control preceding seizure evolution , 2016 .

[96]  William H Theodore,et al.  Circadian and circaseptan rhythms in human epilepsy: a retrospective cohort study , 2018, The Lancet Neurology.

[97]  Daniel Sánchez Morillo,et al.  Physiological closed-loop control in intelligent oxygen therapy: A review , 2017, Comput. Methods Programs Biomed..

[98]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[99]  Kareem A. Zaghloul,et al.  Large-Scale Communication in the Human Brain Is Rhythmically Modulated through Alpha Coherence , 2019, Current Biology.

[100]  M. Avoli,et al.  Jasper's basic mechanisms of the epilepsies , 2012 .

[101]  F. Wendling,et al.  Temporal lobe epilepsy , 2019, Radiopaedia.org.